T-cell based immunotherapy is a rapidly growing field that has experienced impressive clinical anti-cancer successes in the last few years. In particular, it is now possible to generate human T cells that display desired specificities and enhanced functionalities compared with the natural immune system. Ex vivo expansion and activation of T cells are pre-requisites for any form of T cell immunotherapy. Several expansion and activation methodologies have been developed including (i) use of IL-2 to expand Tumor Infiltrating lymphocytes (TILs) isolated from solid tumors, (ii) use of antigen presenting cells, and (iii) use of anti-CD3 and anti-CD28 to activate chimeric antigen receptor (CAR) T cells. However, widespread utilization of T cell immunotherapies for treatment of malignancies and infectious diseases has been hindered by the lack of rapid, cost-effective, and efficient methods for selecting and expanding clinical-grade, therapeutic T cell products that proliferate and persist in vivo. Accordingly, there remains a need in the art for more robust methodologies for expanding T cell populations having clinical therapeutic potential.